Our current working hypothesis is that alterations in lipoprotein lipase activity either constitute or signal the onset of the inborn error of metabolism leading to genetic obesity. We feel that the work completed this year rules out a primary hyperphagia as the cause. Consequently we plan to concentrate our efforts next year on other factors which could influence LPL activity during early development and factors (such as hormonal and dietary factors) which when altered lead to increased LPL activity, subsequent feeding and eventual obesity. Studies to examine the regulatory role of circulating TG on LPL activity in genetically obese rats implanted with chronic catheters are also planned.